Age-adjusted Relative Telomere Length Research Articles

Association study of leukocyte telomere length and genetic polymorphism within hTERT promoter with type 2 diabetes in Bangladeshi population.

Telomeres are protective cap on the ends of DNA of non-coding tandem repeats of TTAGGG. Human telomerase reverse transcriptase (hTERT) is a catalytic subunit of telomerase that maintains the structure of telomeres. Type 2 diabetes (T2D) affects multi-organ and telomere length by altering telomerase activity. We aimed to evaluate the relative telomere length (RTL) and risk association of rs2853669 with T2D in Bangladeshi population. RTL was measured in 408 unrelated Bangladeshi (224 T2D and 184 healthy) using primers for target gene and reference gene albumin. Genotypic frequencies for rs2853669 were determined using TaqMan® probes. The mean level of age adjusted RTL (AARTL) varied significantly between the healthy and individuals with T2D for all the genotypes with respect to rs2853669. Moreover, healthy individuals had significantly higher AARTL than T2D. Similar findings were observed when study participants were stratified based on their gender. Association studies revealed that under codominant model of inheritance, TC genotype showed protective role against development of type 2 diabetes. This study suggests a possible role of telomere biology in T2DM, but their association needs to be evaluated further with a larger series and matched healthy controls.

Relative Telomere Length in Peripheral Blood Cells and Hypertension Risk among Mine Workers: A Case-Control Study in Chinese Coal Miners.

Hypertension is a common chronic disease in middle-aged and elderly people and is an important risk factor for many cardiovascular diseases. Its pathogenesis remains unclear. Epidemiological studies have found that the loss of telomere length in peripheral blood cells can increase the risk of coronary heart disease, myocardial infarction, and other diseases. However, a correlation between loss of telomere length and hypertension has not been established. In this study, we aimed to explore the association between telomere length and the risk of essential hypertension (EH) in Chinese coal miners. A case-control study was performed with 215 EH patients and 222 healthy controls in a large coal mining group located in North China. Face-to-face interviews were conducted by trained staff with the necessary medical knowledge. Relative telomere length (RTL) was measured by a quantitative real-time PCR assay using DNA extracted from peripheral blood. In the control group, the age-adjusted RTL was statistically significantly lower in miners performing hard physical labour compared with nonphysical labour (P = 0.043). A significantly shorter age-adjusted RTL was found in the control group of participants who consumed alcohol regularly compared with those who do not consume alcohol (P = 0.024). Age-adjusted RTL was negatively correlated with body mass index (BMI) and alcohol consumption. Hypertension was also found to be significantly correlated with factors such as age, BMI, alcohol consumption, smoking, and tea consumption. Our results suggest that RTL is associated with hypertension in coal miners.

One-carbon metabolites and telomere length in a prospective and randomized study of B- and/or D-vitamin supplementation.

Vitamin B deficiency is common in elderly people and has been associated with an increased risk of developing age-related diseases. B-vitamins are essential for the synthesis and stability of DNA. Telomers are the end caps of chromosomes that shorten progressively with age, and short telomers are associated with DNA instability. In the present randomized intervention study, we investigated whether the one-carbon metabolism is related to telomere length, a surrogate marker for cellular aging. Sixty-five subjects (>54years) were randomly assigned to receive either a daily combination of vitamin D3 (1200IU), folic acid (0.5mg), vitamin B12 (0.5mg), vitamin B6 (50mg) and calcium carbonate (456mg) (group A) or vitamin D3 and calcium carbonate alone (group B). Blood testing was performed at baseline and after 1year of supplementation. The concentrations of several metabolites of the one-carbon pathway, as well as relative telomere length (RTL) and 5,10-methylenetetrahydrofolate reductase C677T genotype, were analyzed. At baseline, age- and gender-adjusted RTL correlated with total folate and 5-methyltetrahydrofolate (5-methylTHF). Subjects with RTL above the median had higher concentrations of total folate and 5-methylTHF compared to subjects below the median. At study end, gender- and age-adjusted RTL correlated in group A with methylmalonic acid (MMA; r=-0.460, p=0.0012) and choline (r=0.434, p=0.0021) and in group B with 5,10-methenyltetrahydrofolate (r=0.455, p=0.026) and dimethylglycine (DMG; r=-0.386, p=0.047). Subjects in the group A with RTL above the median had lower MMA and higher choline compared to subjects below the median. The present pilot study suggests a functional relationship between one-carbon metabolism and telomere length. This conclusion is supported by several correlations that were modified by B-vitamin supplementation. In agreement with our hypothesis, the availability of nucleotides and methylation groups seems to impact telomere length. Due to the small sample size and the limitations of the study, further studies should confirm the present results in a larger cohort.

Shorter telomeres in adults with Type 1 diabetes correlate with diabetes duration, but only weakly with vascular function and risk factors

ObjectiveTo determine if white blood cell (WBC) telomeres are shorter in Type 1 diabetes (T1D) than in subjects without diabetes (non-DB), and shorter in T1D subjects with vs. without vascular complications; and to determine associations with vascular biomarkers. Research design and methodsWBC relative telomere length (RTL) was determined by quantitative PCR in a cross-sectional study of 140 non-DB and 199 T1D adults, including 128 subjects without vascular complications (T1DNoCx) and 71 subjects with vascular complications (T1DCx). Relationships of RTL with age, T1D duration, arterial elasticity, pulse pressure and vascular risk factors were determined. ResultsRTL did not differ by gender within T1D and non-DB groups. Age-adjusted RTL was shorter in T1D vs. non-DB subjects (1.48±0.03 AU vs. 1.64±0.04 AU, p=0.002), but did not differ by T1D complication status (T1DNoCX 1.50±0.04 vs. T1DCX 1.46±0.05, p=0.50), nor correlate with arterial elasticity. Univariate analysis in T1D showed RTL correlated (inversely) with age r=−0.27, p=0.0001, T1D duration r=−0.16, p=0.03, and pulse pressure (r=−0.15, p=0.04), but not with HbA1c, BP, renal function (serum creatinine, ACR, eGFR), lipids, insulin sensitivity, inflammation (CRP, CAMs) or oxidative stress (OxLDL, OxLDL/LDL-C, MPO, PON-1). Multiple regression analysis showed independent determinants of RTL were age and T1D presence (r=0.29, p<0.0001). ConclusionsIn this cross-sectional study telomeres were shorter in T1D. RTL correlated inversely with T1D duration, but did not differ by complication status and weakly correlated with pulse pressure and vascular risk factors. Only age and T1D were independent determinants of RTL. Longitudinal studies are merited.

Relative telomere lengths in tumor and normal mucosa are related to disease progression and chromosome instability profiles in colorectal cancer.

Telomeric dysfunction is linked to colorectal cancer (CRC) initiation. However, the relationship of normal tissue and tumor telomere lengths with CRC progression, molecular features and prognosis is unclear. Here, we measured relative telomere length (RTL) by real-time quantitative PCR in 90 adenomas (aRTL), 419 stage I-IV CRCs (cRTL) and adjacent normal mucosa (nRTL). Age-adjusted RTL was analyzed against germline variants in telomere biology genes, chromosome instability (CIN), microsatellite instability (MSI), CpG island methylator phenotype (CIMP), TP53, KRAS, BRAF mutations and clinical outcomes. In 509 adenoma or CRC patients, nRTL decreased with advancing age. Female gender, proximal location and the TERT rs2736100 G allele were independently associated with longer age-adjusted nRTL. Adenomas and carcinomas exhibited telomere shortening in 79% and 67% and lengthening in 7% and 15% of cases. Age-adjusted nRTL and cRTL were independently associated with tumor stage, decreasing from adenoma to stage III and leveling out or increasing from stage III to IV, respectively. Cancer MSI, CIMP, TP53, KRAS and BRAF status were not related to nRTL or cRTL. Near-tetraploid CRCs exhibited significantly longer cRTLs than CIN- and aneuploidy CRCs, while cRTL was significantly shorter in CRCs with larger numbers of chromosome breaks. Age-adjusted nRTL, cRTL or cRTL:nRTL ratios were not associated with disease-free or overall survival in stage II/III CRC. Taken together, our data show that both normal mucosa and tumor RTL are independently associated with CRC progression, and highlight divergent associations of CRC telomere length with tumor CIN profiles.

Effect of vegetable consumption on the association between peripheral leucocyte telomere length and hypertension: a case–control study

ObjectivesPeripheral leucocyte telomere length has been suggested to be inversely associated with hypertension risk. Both telomere length and hypertension risk can be modified by certain dietary factors, such as fruit...

Factors influencing telomere length in BRCA-mutation carriers.

e12584 Background: Lifestyle mediators of sporadic breast cancer (BC) risk include physical inactivity, obesity and dysmetabolism. Little is known about the influence of these factors on genetically mediated BC risk. Increasingly, telomere length is being investigated as a biomarker of accumulated cellular damage that may be influenced by lifestyle behaviors. We report results from an ongoing prospective investigation of factors influencing breast cancer risk in BRCA1/2-mutation carriers unaffected by BC examining the association between telomere length and lifestyle factors. Methods: Female BRCA1/2-mutation carriers unaffected by BC were recruited from St James’s Hospital Dublin Ireland. Fasting blood samples were drawn to measure metabolic profile (insulin, glucose glycosylated haemoglobin A1c (HBA1C) and lipid profile) and peripheral blood mononuclear cells (PBMCs). Telomere length was measured from DNA isolated from PBMCs. Body composition was assessed by body mass index and waist circumference and physical activity was assessed objectively by accelerometry and subjectively by the Minnesota Leisure Time Physical Activity Questionnaire. Associations were examined by correlation analysis. Results: To date, data has been analyzed from 73 participants (mean age 42.8 (9.3) years). Over two-thirds of participants were either overweight (37%) or obese (34%) and 72% were centrally obese (waist circumference > 80cm). Metabolic syndrome was diagnosed in 24% of participants and 93% were physically inactive. An association was observed between age-adjusted relative telomere length and measures of dysmetabolism including prevalence of metabolic syndrome features (r = 0.43, p = 0.01) and HBA1c (r = 0.4, p = 0.03). No association was observed between telomere length and either body composition or physical activity. Conclusions: Unhealthy lifestyle patterns (physical inactivity, overweight, obesity and metabolic syndrome) are evident in this Irish cohort of BRCA-mutation carriers. An association between dysmetabolism and shorter telomere length was observed in this population. This may indicate a mechanism through which the consequences of an unhealthy lifestyle influence BC risk and warrants prospective investigation.